GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells.

Journal Article (Journal Article)

Glucose-dependent insulinotropic polypeptide (GIP) communicates nutrient intake from the gut to islets, enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on β cells. The GIPR is also expressed in α cells, and GIP stimulates glucagon secretion; however, the role of this action in the postprandial state is unknown. Here, we demonstrate that GIP potentiates amino acid-stimulated glucagon secretion, documenting a similar nutrient-dependent action to that described in β cells. Moreover, we demonstrate that GIP activity in α cells contributes to insulin secretion by invoking paracrine α to β cell communication. Last, specific loss of GIPR activity in α cells prevents glucagon secretion in response to a meal stimulus, limiting insulin secretion and driving glucose intolerance. Together, these data uncover an important axis by which GIPR activity in α cells is necessary to coordinate the optimal level of both glucagon and insulin secretion to maintain postprandial homeostasis.

Full Text

Duke Authors

Cited Authors

  • El, K; Gray, SM; Capozzi, ME; Knuth, ER; Jin, E; Svendsen, B; Clifford, A; Brown, JL; Encisco, SE; Chazotte, BM; Sloop, KW; Nunez, DJ; Merrins, MJ; D'Alessio, DA; Campbell, JE

Published Date

  • March 2021

Published In

Volume / Issue

  • 7 / 11

PubMed ID

  • 33712466

Pubmed Central ID

  • PMC7954443

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.abf1948


  • eng

Conference Location

  • United States